This invention relates to novel compositions comprising benzoylecgonine and structurally related compounds, and methods for producing them.
Compositions comprising benzoylecgonine and structurally-related chemical compounds (such as ecgonine, ecgonidine and derivative thereof) are useful in preventing and treating a number of important diseases and disorders (see, for example, U.S. Pat. Nos. 4,469,700; 4,512,996; 4,556,663; 5,376,667; 5,559,123 and 5,663,345; each of which is hereby incorporated herein in its entirety). Particularly useful benzoylecgonine-related compounds include the 2-hydroxypropyl ester derivatives of benzoylecgonine, ecgonine, and ecgonidine. Methods for producing compositions comprising these 2-hydroxypropyl esters have been described in U.S. Pat. No. 5,376,667. The preferred method described in U.S. Pat. No. 5,376,667 utilizes the step of heating cocaine base in a propylene glycol/water solution (95% propylene glycol/5% water w/w) at 50xc2x0 C. for 12 days, after which time less than 0.1% of the cocaine base starting material remained (see column 7, lines 3-17). The composition produced by this method comprises approximately 5% w/w of an active component mixture in propylene glycol, wherein the active component mixture comprises approximately 65% benzoylecgonine, 2% ecgonidine and 5% and 6%, respectively, of the 2-hydroxypropyl derivatives of benzoylecgonine and ecgonidine. It has recently been discovered by the inventors hereof that removal of water during the reaction used to produce the 2-hydroxypropyl derivatives of benzoylecgonine and ecgonidine helps drive the reaction to the desired products and, furthermore, removal of water during or subsequent to the reaction results in a composition with enhanced stability. The novel method for the production of the compositions comprising 2-hydroxypropyl derivatives of benzoylecgonine and ecgonidine and the enhanced stability of the resulting composition may provide advantages over the prior art methods and compositions that can be appreciated by one of skill in the art.
The invention described herein fulfills the needs described above. In one embodiment, this invention provides a method for preparing a benzoylecgonine composition comprising the steps of:
(a) contacting benzoylmethylecgonine and propylene glycol in the presence or absence of water to form a reaction mixture;
(b) maintaining the reaction mixture at a temperature between about 50xc2x0 and 100xc2x0 C; and
(c) subsequently or simultaneously removing water from the reaction mixture.
In another embodiment, this invention provides novel benzoylecgonine compositions comprising at least about 2% 2-hydroxypropyl benzoylecgonine esters, at least about 2% 2-hydroxypropyl ecgonidine esters, less than about 0.1% benzoylmethylecgonine and between about 0% and about 4% water.
The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims.